| First Author | Baharom F | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 1 | Pages | 41-52 |
| PubMed ID | 33139915 | Mgi Jnum | J:305905 |
| Mgi Id | MGI:6706673 | Doi | 10.1038/s41590-020-00810-3 |
| Citation | Baharom F, et al. (2021) Intravenous nanoparticle vaccination generates stem-like TCF1(+) neoantigen-specific CD8(+) T cells. Nat Immunol 22(1):41-52 |
| abstractText | Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoantigen-specific CD8(+) T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1(+)PD-1(+)CD8(+) T cells as compared to subcutaneous immunization (SNP-SC). Single-cell RNA sequencing showed that SNP-IV induced stem-like genes (Tcf7, Slamf6, Xcl1) whereas SNP-SC enriched for effector genes (Gzmb, Klrg1, Cx3cr1). Stem-like cells generated by SNP-IV proliferated and differentiated into effector cells upon checkpoint blockade, leading to superior antitumor response as compared to SNP-SC in a therapeutic model. The duration of antigen presentation by dendritic cells controlled the magnitude and quality of CD8(+) T cells. These data demonstrate how to optimize antitumor immunity by modulating vaccine parameters for specific generation of effector or stem-like CD8(+) T cells. |
